Hypertensive Organ Damage Research Articles

Prolonged Time-to-antihypertensive Therapy Worsens Organ Damage and Blood Pressure Control in Arterial Hypertension.

Delay in arterial hypertension (AH) diagnosis and late therapy initiation may affect progression towards hypertensive-mediated organ damage (HMOD) and blood pressure (BP) control. We aimed to assess the impact of time-to-therapy on BP control and HMOD in patients receiving AH diagnosis. We analysed data from the Campania Salute Network, a prospective registry of hypertensive patients (NCT02211365). At baseline visit, time-to-therapy was defined as the interval between the first occurrence of BP values exceeding guidelines-directed thresholds and therapy initiation; HMOD included left ventricular hypertrophy (LVH), carotid plaque, or chronic kidney disease. Optimal BP control was considered for average values < 140/90 mmHg. Low-risk profile was defined as grade I AH without additional cardiovascular risk factors. From 14,161 hypertensive patients, we selected 1,627 participants who were not on antihypertensive therapy. This population was divided into two groups based on the median time-to-therapy (≤ 2 years n = 1,009, > 2 years n = 618). Patients with a time-to-therapy > 2 years had higher risk of HMOD (adjusted odds ratio, aOR:1.51, 95%, CI:1.19-1.93, p < 0.001) due to increased risks of LVH (aOR:1.43, CI:1.12-1.82, p = 0.004), carotid plaques (aOR:1.29, CI:1.00-1.65, p = 0.047), and chronic kidney disease (aOR:1.68, CI:1.08-2.62, p = 0.022). Time-to-therapy > 2 years was significantly associated with uncontrolled BP values (aOR:1.49, CI:1.18-1.88, p < 0.001) and higher number of antihypertensive drugs (aOR:1.68, CI:1.36-2.08, p < 0.001) during follow-up. In low-risk subgroup, time-to-therapy > 2 years did not impact on BP control and number of drugs. In hypertensive patients, a time-to-therapy > 2 years is associated with HMOD and uncontrolled BP.

Neuroimmune modulation for targeting organ damage in hypertension and atherosclerosis.

The brain is essential for processing and integrating sensory signals coming from peripheral tissues. Conversely, the autonomic nervous system regulated by brain centres modulates the immune responses involved in the genesis and progression of cardiovascular diseases. Understanding the pathophysiological bases of this relationship established between the brain and immune system is relevant for advancing therapies. An additional mechanism involved in the regulation of cardiovascular function is provided by the brain-mediated control of the renin-angiotensin system. In both cases, the communication is typically bidirectional and established by afferent and sensory signals collected at the level of peripheral tissues, efferent circuits, as well as of hormones. Understanding how the brain mediates the bidirectional communication and how the immune system participates in this process is object of intense investigation. This review examines key findings that support a role for these interactions in the pathogenesis of major vascular diseases that are characterized by a consistent alteration of the immune response, such as hypertension and atherosclerosis. In addition, we provide a critical appraisal of the translational implications that these discoveries have in the clinical setting where an effective management of neuroimmune and/or neuroinflammatory state might be beneficial.

O100 IL15RA MEDIATES BLOOD PRESSURE ELEVATION, INFLAMMATION AND VASCULAR DAMAGE IN ANGIOTENSIN II-INDUCED HYPERTENSION

Cytokines are key mediators regulating blood pressure (BP) and target organ damage in hypertension. IL15 levels increase in cardiovascular diseases, but the role of IL15 and its receptor alpha (IL15R) in hypertension and hypertension-mediated inflammation and vascular damage is still unknown. Wild-type and IL15Rα-/-mice (n=5-9) were infused with vehicle or angiotensin II (AngII, 490ng/min/kg). Recombinant IL15 was administered to WT mice (1ug, daily, 14 days) during AngII infusion. Telemetry, wire myography, luminometry, PSR staining, qPCR, immunoblotting, flow cytometry, and primary cell lines were used. Hypertensive patients have increased levels of IL15Rα in arteries, which significantly correlated with systolic (r=0.33, p=0.002), diastolic (r=0.27, p=0.02) pressure and maximal constriction to phenylephrine ex vivo (r=0.27, p=0.03). Similarly, AngII infusion significantly increased serum IL15/IL15Rα (8.8±0.7pg/ml vs 12.1±0.7pg/ml, p&lt;0.01), IL15Rα mRNA (1±0.1 vs 1.8±0.1, p&lt;0.01) and protein (1±0.03 vs 1.8±0.28, p&lt;0.01) levels in the aortas. BP lowering using hydralazine and hydrochlorothiazide treatment prevented these changes in vasculature. IL15Rα was induced by pathophysiological stretch (15%) or interferon-gamma in adventitial fibroblasts, vascular smooth muscles, and endothelial cells in vitro. In contrast, AngII, other inflammatory cytokines or oxidative stress mediators have no such direct effect. Il15Rα-/- blunted AngII-induced hypertension (199±5.6mmHg vs 148±7.3mmHg, p&lt;0.001), protected against endothelial dysfunction (p&lt;0.01) and aortic superoxide production (59.4±7.8 vs 36.4±7.6 RLU/sec/mg) compared to wild-type mice. This was accompanied by reduced perivascular inflammation, lack of immune cell recruitment and effector and memory T cell formation. Similarly, T cell interferon-gamma and interleukin-17 production was attenuated in Il15Rα-/- hypertensive mice. In contrast, simultaneous administration of AngII and rIL15 into WT mice enhanced these outcomes. Perivascular fibrosis was observed in WT, but not Il15Rα-/- hypertensive animals (111036±19117 μm2 vs 48689±5515 μm2, p&lt;0.01) and was in line with significantly lower mRNA of collagen and fibronectin protein levels in Il15Rα-/- aortas. IL15Rα plays a crucial role in immune activation, vascular damage, and AngII-induced hypertension. Targeting this pathway may offer potential therapeutic benefits for controlling hypertension and preventing associated vascular complications.

Abstract P108: Correlations of attended and unattended office blood pressure measurements with Left Ventricular Mass in untreated hypertensives.

Introduction: Unattended (UA) office blood pressure (BP) measurements have been proposed as better substitutes for attended (AT) BP readings for the diagnosis and monitoring of patients with hypertension (HTN). A superior correlation of UA over AT BP measurements with Left Ventricular Hypertrophy (LVH), an early marker of hypertensive organ damage has not been conclusively demonstrated. We hypothesized that in a group with untreated HTN, UA BP would correlate more strongly with left ventricular hypertrophy than AT BP. Methods: Newly diagnosed untreated patients with HTN presenting newly to an outpatient clinic in Nigeria were consented as part of a larger study. Three sets of AT and UA seated BP readings were carried out using a validated device followed by same-day echocardiographic assessment of their Left Ventricular Mass Indexed to Body surface area (LVMI). Pearson’s coefficient (r) was determined and a 2-tailed significance was defined by a two-tailed P value (P) less than 0.05. Coefficients were compared using Fisher r to z transformation. Results: A total of 49 participants (female=25) were recruited with a mean age of 46.2 +/- 9 years. The mean of the AT BP in the cohort (mAT) was 157.1 +/- 13.5mmHg, while the mean of the UA BP was 151.9 +/- 15.7 with no significant difference in both (P=0.085). The mean LVMI of the cohort was 102.3 +/- 28.7 mg/m2. Both the mAT BP (r= 0.304, P= 0.034) and the mUA BP (r=0.354, P=0.013) positively correlated with LVMI, with no significant difference in the strength of both correlations with r to z transformation (z=0.27, P=0.394 ). Conclusion: In a small cohort of newly diagnosed Nigerian hypertensives, both attended and unattended systolic office blood pressure readings correlated positively with left ventricular mass indexed to body surface area, with no significant difference in the strength of their correlation. Having failed to demonstrate a superior correlation of unattended blood pressure readings with LVH, our findings support the continued use of attended office blood pressure readings for clinical monitoring in busy time-constrained office settings where unattended office blood pressure monitoring may not be feasible. Larger studies are however required to confirm these findings.

Abstract P155: Elevated Long-Term Triglyceride-to-High Density Lipoprotein Cholesterol Ratio Variability From Childhood Is Linked To Higher Risk Of Early-Onset Hypertension: The Bogalusa Heart Study

Background: Early-onset hypertension is linked to higher risk of hypertensive organ damage compared to late-onset hypertension. Insulin resistance has been shown to be associated with greater risk of hypertension. Greater triglyceride-to-high density lipoprotein cholesterol ratio (TG/HDL-C), a surrogate marker of insulin resistance, has been linked to higher risk of hypertension. However, whether elevated long-term TG/HDL-C variability from childhood is associated with higher risk of early-onset hypertension is unclear. Methods: We studied 1271 participants of the Bogalusa Heart Study (age at enrollment: 9.9 ± 4.0 years, follow-up : 38.3 ± 3.8 years, age at last exam: 48.2 ± 5.2 years, 59.5% women, 34.4% Black participants) with ≥3 lipid measurements during follow-up. TG/HDL-C was obtained as TG (mg/dL) divided by HDL-C (mg/dL). Onset of hypertension was defined as blood pressure ≥140/90 mmHg or taking antihypertensive medications detected during follow-up. According to age at onset of hypertension, 4 subgroups were formed: &lt;35 years (early-onset hypertension), 35-44 years, ≥45 years, and people without hypertension. Long-term TG/HDL-C variability from childhood was calculated as the deviation from age predicted values (DEV) and residual SD (RSD). DEV and RSD were obtained from the growth curves derived from linear mixed effect models, as the mean and SD of the residuals of observed and predicted TG/HDL-C levels. Associations between TG/HDL-C variability and hypertension onset subgroups were evaluated using multinomial logistic regression models. People who did not have hypertension during follow-up were the reference group. Interactions by race and sex were performed. Results: Among the 1271 participants, 585 (46.0%) had hypertension at last exam; among the 585, 124 (21.2%) had early-onset hypertension. For 1 SD increase in DEV and RSD of TG/HDL-C, the odds of early-onset hypertension increased by 30.6% (95% CI 1.06, 1.61) and 28.8% (95% CI 1.06,1.57), compared to people without hypertension, after adjusting for race, sex, diabetes, obesity, and smoking status, education, and TG/HDL-C at last exam. No significant associations were observed between DEV and RSD of TG/HDL-C and other hypertension onset subgroups. No significant interactions were found between both DEV and RSD and race and sex. Conclusions: Our results suggest that individuals with higher long-term variability in insulin resistance may be at a greater risk of having early-onset hypertension.

Effect of early endothelial function improvement on subclinical target organ damage in hypertensives

Endothelial dysfunction is acknowledged as a marker for subclinical target organ damage (STOD) in hypertension, though its therapeutic potential has not yet been clarified. This study assessed whether early endothelial function improvement (EEFI) reduced STOD in patients with essential hypertension (EH). We conducted a retrospective cohort analysis of 456 EH patients initially free from STOD. Endothelial function was assessed using brachial artery flow-mediated dilation (FMD), with values ≤ 7.1% indicating dysfunction. Patients were initially categorized by endothelial status (dysfunction: n = 180, normal: n = 276), and further divided into improved or unimproved groups based on changes within three months post-enrollment. During a median follow-up of 25 months, 177 patients developed STOD. The incidence of STOD was significantly higher in patients with initial dysfunction compared to those with normal function. Kaplan–Meier analysis indicated that the improved group had a lower cumulative incidence of STOD compared to the unimproved group (p < 0.05). Multivariable Cox regression confirmed EEFI as an independent protective factor against STOD in EH patients (p < 0.05), regardless of their baseline endothelial status, especially in those under 65 years old, non-smokers, and with low-density lipoprotein cholesterol levels ≤ 3.4 mmol/L. In conclusion, EEFI significantly reduces STOD incidence in EH patients, particularly in specific subgroups, emphasizing the need for early intervention in endothelial function to prevent STOD.

Arterial stiffness in non-alcoholic fatty liver disease

Background. The presence of metabolic-associated pathology, namely obesity, diabetes mellitus, dyslipidemia, and non-alcoholic fatty liver disease (NAFLD), significantly accelerates the development of the cardiovascular continuum. This is associated with an increased risk of major cardiovascular events (myocardial infarction, stroke). An important organ damage in hypertension (HTN) is the remodeling of small arteries and an increase in stiffness of large arteries. The relationship between NAFLD, dyslipidemia, hypertriglyceridemia, obesity (especially abdominal), diabetes, and HTN is well studied, but there is a lack of clinical studies examining changes in arterial stiffness in NAFLD. Aim of the research was to study the parameters of arterial stiffness in patients with NAFLD. Materials and methods. Eighty-two Caucasian patients with NAFLD (mean age (56.8 ± 1.1) years, 59.8 % men) were enrolled. Participants were divided into two groups: group 1 (n = 44) — NAFLD and concomitant HTN, group 2 (n = 38) — HTN without NAFLD. All patients underwent a standard general clinical examination, laboratory and instrumental work-up. In addition, all patients were assessed for the parameters of arterial stiffness via non-invasive arteriography. Results. Patients with NAFLD had significantly higher office systolic and diastolic blood pressure (by 15.2 and 10.4 %, respectively, p &lt; 0.01) despite comparable drug therapy. The same trends were observed in relation to the central aortic pressure, which was 19.3 % higher in patients with NAFLD (p &lt; 0.01), and central pulse pressure that was 35.9 % higher than in patients without NAFLD (p &lt; 0.01). Brachial artery augmentation index in NAFLD turned to be elevated compared to patients without NAFLD (p &lt; 0.01), but aortic augmentation index was comparable between groups. The return time interval in group 1 was 50.3 % higher than in group 2 (p &lt; 0.01). Finally, patients with NAFLD had a significant increase in pulse wave velocity by 52.3 % compared to those without NAFLD with average value exceeding 12 m/sec (p &lt; 0.01). Conclusions. There is an association between NAFLD and worse indices of arterial stiffness in patients with concomitant HTN.

The Participation of Ferroptosis in Fibrosis of the Heart and Kidney Tissues in Dahl Salt-Sensitive Hypertensive Rats.

Salt-sensitive hypertension is often more prone to induce damage to target organs such as the heart and kidneys. Abundant recent studies have demonstrated a close association between ferroptosis and cardiovascular diseases. Therefore, we hypothesize that ferroptosis may be closely associated with organ damage in salt-sensitive hypertension. This study aimed to investigate whether ferroptosis is involved in the occurrence and development of myocardial fibrosis and renal fibrosis in salt-sensitive hypertensive rats. Ten 7-week-old male Dahl salt-sensitive (Dahl-SS) rats were adaptively fed for 1 week, then randomly divided into two groups and fed either a normal diet (0.3% NaCl, normal diet group) or a high-salt diet (8% NaCl, high-salt diet group) for 8 weeks. Blood pressure of the rats was observed, and analysis of the hearts and kidneys of Dahl-SS rats was conducted via hematoxylin-eosin (HE) staining, Masson staining, Prussian blue staining, transmission electron microscopy, tissue iron content detection, malondialdehyde content detection, immunofluorescence, and Western blot. Compared to the normal diet group, rats in the high-salt diet group had increases in systolic blood pressure and diastolic blood pressure (P < 0.05); collagen fiber accumulation was observed in the heart and kidney tissues (P < 0.01), accompanied by alterations in mitochondrial ultrastructure, reduced mitochondrial volume, and increased density of the mitochondrial double membrane. Additionally, there were significant increases in both iron content and malondialdehyde levels (P < 0.05). Immunofluorescence and Western blot results both indicated significant downregulation (P < 0.05) of xCT and GPX4 proteins associated with ferroptosis in the high-salt diet group. Ferroptosis is involved in the damage and fibrosis of the heart and kidney tissues in salt-sensitive hypertensive rats.

#2683 Targeted antibiotic modulation of the gut microbiome ameliorates hypertensive kidney damage

Abstract Background and Aims High blood pressure is associated with measurable inflammation, which precedes and promotes damage to the heart and kidneys. Microbiome-derived metabolites, particularly indole metabolites, modulate inflammation and host physiology, partially through aryl hydrocarbon receptor (AhR) signaling. To better understand the potential of a microbiome-targeting therapeutic approach to achieve organ protection in hypertension, we used narrow-spectrum antibiotics without enteral absorption to specifically deplete gram-negative or -positive bacteria in double transgenic rats (dTGR). Method Four-week-old dTGR (transgenic for human renin and angiotensinogen) were treated with oral Vancomycin (Vanco), Polymyxin B (Poly) or Vehicle (Veh) for 3 weeks. Seven-week-old SD rats were included as healthy controls. Microbiome, clinical and immune phenotype were analyzed by shotgun metagenomic sequencing, echocardiography, telemetric blood pressure (BP) measurement, clinical chemistry, bulk RNAseq and flow cytometry. Results Hypertensive kidney damage was ameliorated in Vanco treated dTGR, as assessed by renal Lcn2 expression, blood urea nitrogen and albuminuria. Vanco treated dTGR had significantly decreased cardiac hypertrophy. Poly treatment showed no effect. BP levels for both antibiotic treatments were not significantly different from Veh, despite a significantly improved endothelium-dependent and -independent vasorelaxation in isolated mesenteric arteries in both treated groups. Surprisingly, Vanco treatment led to a massive increase of gram-positive Lactobacilli and associated gene abundance for the production of indole lactic acid (ILA, via araT). We could previously show that ILA inhibits differentiation of pathological Th17 cells through AhR modulation. In line, Vanco treatment reduced the increased number of pathological Th17 in the kidney and intestine of dTGR. Poly treatment did not alter the inflammatory signature. Conclusion Modulation of the intestinal microbiome by narrow-spectrum antibiotics affects hypertensive organ damage. Our data underscores the importance of the gut microbiome in modulating hypertensive organ damage and helps to identify potential therapeutic strategies in the microbiome. Ongoing experiments investigate pro- and postbiotic therapeutic approaches and their AhR dependency.

Possible Role of Gut Microbiota Alterations in Myocardial Fibrosis and Burden of Heart Failure in Hypertensive Heart Disease.

Epidemiological studies have revealed that hypertensive heart disease is a major risk factor for heart failure, and its heart failure burden is growing rapidly. The need to act in the face of this threat requires first an understanding of the multifactorial origin of hypertensive heart disease and second an exploration of new mechanistic pathways involved in myocardial alterations critically involved in cardiac dysfunction and failure (eg, myocardial interstitial fibrosis). Increasing evidence shows that alterations of gut microbiota composition and function (ie, dysbiosis) leading to changes in microbiota-derived metabolites and impairment of the gut barrier and immune functions may be involved in blood pressure elevation and hypertensive organ damage. In this review, we highlight recent advances in the potential contribution of gut microbiota alterations to myocardial interstitial fibrosis in hypertensive heart disease through blood pressure-dependent and blood pressure-independent mechanisms. Achievements in this field should open a new path for more comprehensive treatment of myocardial interstitial fibrosis in hypertensive heart disease and, thus, for the prevention of heart failure.

Frail hypertensive older adults with prediabetes and chronic kidney disease: insights on organ damage and cognitive performance - preliminary results from the CARYATID study

BackgroundHypertension and chronic kidney disease (CKD) pose significant public health challenges, sharing intertwined pathophysiological mechanisms. Prediabetes is recognized as a precursor to diabetes and is often accompanied by cardiovascular comorbidities such as hypertension, elevating the risk of pre-frailty and frailty. Albuminuria is a hallmark of organ damage in hypertension amplifying the risk of pre-frailty, frailty, and cognitive decline in older adults. We explored the association between albuminuria and cognitive impairment in frail older adults with prediabetes and CKD, assessing cognitive levels based on estimated glomerular filtration rate (eGFR).MethodsWe conducted a study involving consecutive frail older patients with hypertension recruited from March 2021 to March 2023 at the ASL (local health unit of the Italian Ministry of Health) of Avellino, Italy, followed up after three months. Inclusion criteria comprised age over 65 years, prior diagnosis of hypertension without secondary causes, prediabetes, frailty status, Montreal Cognitive Assessment (MoCA) score < 26, and CKD with eGFR > 15 ml/min.Results237 patients completed the study. We examined the association between albuminuria and MoCA Score, revealing a significant inverse correlation (r: 0.8846; p < 0.0001). Subsequently, we compared MoCA Score based on eGFR, observing a significant difference (p < 0.0001). These findings were further supported by a multivariable regression analysis, with albuminuria as the dependent variable.ConclusionsOur study represents the pioneering effort to establish a significant correlation between albuminuria and eGFR with cognitive function in frail hypertensive older adults afflicted with prediabetes and CKD.

Spatiotemporal analysis of the effects of exercise on the hemodynamics of the aorta in hypertensive rats using fluid-structure interaction simulation

Abstract Background and Objective Hemodynamic changes that lead to increased blood pressure represent the main drivers of organ damage in hypertension. Prolonged increases to blood pressure can lead to vascular remodeling, which also affects vascular hemodynamics during the pathogenesis of hypertension. Exercise is beneficial for relieving hypertension, however the mechanistic link between exercise training and how it influences hemodynamics in the context of hypertension is not well understood. Methods n exercise model was developed using spontaneously hypertensive rats (SHR) subject to a 12-week treadmill training regime. The heart rates and blood pressures of rats were measured using the tail cuff method, while micro-computed tomography (CT) scanning was used to develop three-dimensional structures of rat aorta, and ultrasound was used to detect rat aortic blood flow and changes to vessel wall structures. Computational fluid dynamics (CFD) and fluid-structure interaction (FSI) models were used to simulate and measure hemodynamic parameters of the rat aortic vessels. In parallel, Masson staining was performed on fixed samples of blood vessels to investigate collagen volume fraction. Hypertensive rats in the sedentary and long-term exercise training groups were subjected to a single bout exercise training, and their aortic hemodynamic parameters were analyzed before, 5 min, 24 h, and 72 h after the single bout exercise. Results Of the two models, in comparison to actual ultrasonic measurement values recorded, we found that numerical simulation results from the FSI model could more accurately model blood flow in the ascending aorta of hypertensive rats, compared to the CFD model. Moreover, longterm exercise training improved local hemodynamic parameters of blood vessels, and led to improvements in adverse hemodynamic features documented, including time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), and relative residence time (RRT). Longterm exercise training of SHR also improved local vascular collagen deposition in the aorta, while improvements in vascular remodeling were also correlated with favorable hemodynamic parameters. Compared with sedentary SHR, signals for low TAWSS regions of the aortic arch in SHR on the long-term exercise regime shifted to the position of the ascending aorta after a single bout of exercise. Conclusions This study demonstrates that FSI is informative to study the spatiotemporal effects of long-term exercise training on hemodynamic changes within the aortas of hypertensive rats, and that long-term exercise is beneficial through its effects to modulate vascular hemodynamics in hypertension.

Hypertensive rats show increased renal excretion and decreased tissue concentrations of glycine betaine, a protective osmolyte with diuretic properties.

Hypertension leads to water-electrolyte disturbances and end-organ damage. Betaine is an osmolyte protecting cells against electrolyte imbalance and osmotic stress, particularly in the kidneys. This study aimed to evaluate tissue levels and hemodynamic and renal effects of betaine in normotensive and hypertensive rats. Betaine levels were assessed using high-performance liquid chromatography-mass spectrometry (HPLC-MS) in normotensive rats (Wistar-Kyoto, WKYs) and Spontaneously Hypertensive rats (SHRs), a model of genetic hypertension. Acute effects of IV betaine on blood pressure, heart rate, and minute diuresis were evaluated. Gene and protein expression of chosen kidney betaine transporters (SLC6a12 and SLC6a20) were assessed using real-time PCR and Western blot. Compared to normotensive rats, SHRs showed significantly lower concentration of betaine in blood serum, the lungs, liver, and renal medulla. These changes were associated with higher urinary excretion of betaine in SHRs (0.20 ± 0.04 vs. 0.09 ± 0.02 mg/ 24h/ 100g b.w., p = 0.036). In acute experiments, betaine increased diuresis without significantly affecting arterial blood pressure. The diuretic response was greater in SHRs than in WKYs. There were no significant differences in renal expression of betaine transporters between WKYs and SHRs. Increased renal excretion of betaine contributes to decreased concentration of the protective osmolyte in tissues of hypertensive rats. These findings pave the way for studies evaluating a causal relation between depleted betaine and hypertensive organ damage, including kidney injury.

Extracellular vesicles mirror the beneficial effect of wild olive (acebuche) oil in hypertensive‐like retinal pigment epithelial cells

Aims/Purpose: Arterial hypertension (AH) leads to oxidative and inflammatory imbalance triggering hypertensive organ damage via different pathways. Oil extracted from the wild olive tree (acebuche, ACE) has previously shown antioxidant and anti‐inflammatory properties against hypertensive ocular damage when regularly consumed in the diet1,2. We therefore speculate that circulating extracellular vesicles (EVs) isolated from ACE oil‐fed animals might play a role in modulating pathological mechanisms surrounding AH‐related ocular diseases, including oxidative stress, migration and angiogenesis processes.Methods: Retinal pigment epithelium (ARPE‐19) cells mimicking a hypertensive phenotype induced by incubation with angiotensin II (AngII) were treated with EVs obtained from mice fed ACE oil or a reference extra virgin olive oil (EVOO). The 2′,7′dichlorodihydrofluorescein diacetate (DCFHDA) assay was used to estimate intracellular levels of reactive oxygen species (ROS). Furthermore, kinetic parameters for L‐arginine (L‐Arg) transport and the expression of L‐Arg transporter (CAT‐1) were also analysed. The wound‐healing assay was used to determine the anti‐migratory properties of ACE oil‐derived EVs, and the ability of EVs to modulate angiogenesis was assessed in aortic rings.Results: Both ACE oil‐ and EVOO‐related EVs were able to reduce ROS production in ARPE‐19 cells. The normalization of intracellular redox status by EVs might be exerted through modulation of L‐Arg uptake and CAT‐1 expression. Anti‐migratory and anti‐angiogenesis properties were also displayed by oil‐derived EVs, suggesting their potential benefit in the setting of neovascular ocular diseases.Conclusions: This is the first report to highlight the retinoprotective effects of EVs isolated from the plasma of animals subjected to ACE oil‐ and EVOO‐enriched diets against pathological events related to ocular diseases.

Abstract 15801: Nighttime Hypertension is a Risk Factor for Cardiovascular Events in Stage B Heart Failure Patients

Background: Nighttime blood pressure (BP) was reported to have a stronger association with cardiovascular outcome and hypertensive organ damage than clinic BP, 24-hour BP, and daytime BP in hypertensives. However, the significance of nighttime BP was not established in stage B heart failure (HF) patients. We hypothesized that nighttime BP measured by home BP monitoring device was associated with cardiovascular outcome in stage B HF patients. Method: We used the dataset of Japan Morning Surge-Home Blood Pressure study (J-HOP study), and selected 417 of stage B HF patients. The definition of stage B HF was based on Universal definition of HF. The patients with history of HF hospitalization were excluded. BP was measured on waking, before bedtime and during the night. The cardiovascular event was followed. Result: Mean follow-up period was 6.6±3.8 years, and 59 cardiovascular events were occurred. When nighttime hypertension was defined as nighttime BP &gt;120mmHg, nighttime HT group showed higher BMI, serum creatinine, HbA1c, and higher prevalence of diabetes, atrial fibrillation, and chronic kidney disease, and lower HDL-cholesterol than nighttime normotension (NT) group. With regard to BP, nighttime HT group, clinic BP, home morning BP, home evening BP, and home nighttime BP were higher in nighttime HT group than in nighttime NT group. In Kaplan-Meier analysis, nighttime HT group had a higher incident of cardiovascular event than nighttime NT group (P&lt;0.01). In Cox multivariate analysis, nighttime HT was significant predictor for cardiovascular event adjusting by significant variables (Hazard ratio 1.84, 95% Confidence interval: 1.01-3.36, P=0.046). Conclusions: Nighttime HT was a prognostic factor in stage B HT patients. Nighttime BP was a therapeutic target to improve the outcome in stage B HT patients.

Targeted Antibiotic Modulation of the Gut Microbiome Ameliorates Hypertensive Organ Damage

Targeted Antibiotic Modulation of the Gut Microbiome Ameliorates Hypertensive Organ Damage

Arterial hypertension and stiffness in women of different age groups and reproductive status

Objective: study of the relationship between arterial hypertension and arterial stiffness in women to identify potential markers of target organ damage and therapeutic targets of antihypertensive therapy.Materials and methods: the study involved 161 women who were divided into three groups depending on age and reproductive function. Group 1 consisted of 52 women aged 18 to 30; group 2 – 54 women aged 31 years before menopause; 3rd group – 55 women in the postmenopausal period. All women were questioned, clinical examination, determination of anthropometric data, measurement of carotid-femoral pulse wave velocity, determination of arterial stiffness by volumetric sphygmography, 24-hour blood pressure monitoring with assessment of aortic stiffness and characteristics of the central pulse wave.Results: 24-hour blood pressure monitoring revealed arterial hypertension in 38 (34,8%) women: 15 (27,8%) women in the 2nd group and 23 (41,8%) women in the 3rd group. Correlation analysis revealed the most significant correlations between the presence of arterial hypertension (R=0,45-0,71; p&lt;&lt;0,01) with central aortic pressure, double product index and average daily aortic pulse wave velocity in the aorta (PWVao), regardless of the state reproductive function. For women of reproductive age with arterial hypertension, the ambulatory vascular stiffness index (AASI: R=0,36; p=0,01) is more significant, while in the menopausal period, the arterial stiffness index (ASI: R=0,33; p=0,01). Correlation analysis did not reveal significant relationships between carotid-femoral pulse wave velocity and cardio-ankle vascular index (CAVI) with arterial hypertension in women of the 2nd and 3rd groups. The relationship between carotid-femoral pulse wave velocity and arterial hypertension in women was confirmed by analysis of variance (p=0,007).Conclusion: Central aortic pressure, carotid-femoral pulse wave velocity, AASI, ASI, PWVao – direct and indirect indicators of arterial stiffness – are interconnected with the presence of arterial hypertension in women of reproductive and menopausal age. In this regard, these indicators are potential markers of target organ damage in arterial hypertension.

Left ventricular hypertrophy and mortality in ethnic minority groups in the UK: e-ECHOES study.

Hypertension is the key modifiable cardiovascular risk factor but is underdiagnosed, and its scale in South Asian and African-Caribbean communities is unknown. Left ventricular hypertrophy (LVH) is a measure of target organ damage in uncontrolled hypertension. The study assesses LVH prevalence in South Asian and African-Caribbean communities and its impact on mortality. This study is based on the large prospective UK community Ethnic-Echocardiographic Heart of England Screening Study (E-ECHOES, age ≥45 years). Left ventricular mass index (LVMI) was calculated using echocardiography to establish LVH. The predictive value of LVH all-cause and cardiovascular mortality was assessed using Cox regression. The study included 3200 South Asians (age 59 ± 10 years, 52% women, 45% had a history of hypertension, 5.8 ± 1.0-year follow-up). LVH was found in 1568 (49%), of whom 45% did not have hypertension diagnosis. On Cox regression, LVH was independently associated with all-cause mortality [hazard ratio 1.38, 95% confidence interval (95% CI) 1.01-1.88], cardiovascular mortality (hazard ratio 2.64, 95% CI 1.21-3.73). The projected overall hypertension prevalence was 82%, undiagnosed hypertension prevalence 37%. The study included 1858 African-Caribbeans (age 62 ± 12, 45% women, 45% had history of hypertension, 5.1 ± 0.9-year follow-up). LVH was found in 1186 (64%), of whom 32% did not have hypertension diagnosis. LVH was borderline associated with all-cause mortality (hazard ratio 1.57, 95% CI 1.01-2.44), but not cardiovascular mortality (hazard ratio 1.82, 95% CI 0.80-4.16). The projected overall hypertension prevalence was 78.5%, and undiagnosed hypertension prevalence was 20.8%. UK South Asians and African-Caribbeans have a high prevalence of hypertension, which is often underdiagnosed and poorly controlled.

Abstract P179: Nano- And Microplastic-enriched Diets Affect Inflammation And Target Organ Damage In Hypertension

Plastic particle pollution is a major environmental challenge worldwide. Micro (MP)- and nanoplastic (NP) particles appear ubiquitously and have been detected in food, drinking water, human feces and blood. Once absorbed, plastic particles can alter the gut microbiome and induce inflammation. Current research primarily focuses on the impact on healthy organisms. Yet, a deeper understanding of the impact of MP and NP on health-to-disease transition and their impact on cardiovascular disease is missing. This project aims to investigate the impact of MP and NP in experimental hypertension. Ten-week-old male NMRI mice were randomized to receive the following particle-enriched diets: a polystyrene MP (particle size 5 μm) (20 μg/g chow, 100 μg/l via drinking water), NP (particle size 100nm) (20 μg/g chow,100 μg/l via drinking water) or control (C) for four weeks. Subsequently, hypertension (HTN) was induced by Angiotensin II (AngII) infusion (1000 ng/kg*min s.c., osmotic minipump). Sham-treated non-hypertensive mice served as controls. During hypertension induction mice were continued on their respective diets. After 14 days, we assessed hypertensive organ damage and inflammation. AngII-treated mice developed hypertension an increased cardiac hypertrophy index (Sham vs HTN: 10.1 vs 10.7 mg/mm tibia), and lower cardiac output (HTN vs Sham: 15.5 vs 19.9 ml/min, echocardiography). MP fed mice showed upregulated mRNA expression of marker genes for renal fibrosis ( Ctgf; Acta ) in both homeostasis (ddCT -2 for MP: 2.7; 6.6) and HTN (ddCT -2 3.2 (MP) vs. 2.3 (C); 14.2 (MP) vs 11.2 (C)), as well as enhanced proinflammatory gene expression ( Ccl2; IL1b ) in HTN (ddCT -2 7.4 (MP) vs 4.0 (C); 5.8 (MP) vs 4.3 (C)). Similarly, NP fed mice showed altered mRNA expression for e.g. IL1b (ddCT -2 for NP: 3.6). Flow cytometric analysis shows a proinflammatory immune response to MP and NP, e.g. an increase of circulating neutrophils (HTN C vs. MP: 24.7% vs 50.0% of CD45+) and Ly6C hi monocytes (Homeostasis C vs NP: 2.4 vs 3.2% of CD45+). Conclusion: MP and NP affect the inflammatory response and organ damage in hypertension. Our further investigations will help to shed light on the impact of this ubiquitous environmental influence on hypertension, associated organ damage and the microbiome.

Abstract P189.2: Aberrant Trafficking Of Intestinal Immune Cells In Salt-sensitive Hypertension

Hypertension is characterized by an inflammatory response, which precedes the clinical detection of organ damage. Yet, the activation and origin of target organ infiltrating immune cells are not fully understood. This study takes a systems view on inflammation in experimental hypertension and aims to investigate the extent to which the gut-associated immune cells contribute to the immune response in salt-sensitive hypertension. Immune cell trafficking from the intestine to hypertensive target organs was analyzed using in vivo labelling of intestinal immune cells via targeted UV-photoconversion in Kaede -transgenic mice. Salt-sensitive hypertension was induced in 8-10 week old male mice by oral N-nitro-L-arginine methylester (L-NAME) pretreatment (0.5 mg/ml) and two 3-week high-salt feedings (HSD, 4% NaCl-diet, 1% drinking water), separated by a 2-week normal-salt (NSD, 0.5% NaCl-diet) interval. Hypertensive organ damage and photolabelled immune cells (5d post photoconversion) were analyzed. HSD-fed mice displayed target organ damage as indicated by upregulation of mRNA-expression of markers of kidney damage ( Ngal ), inflammation ( Ccl2 ) and fibrosis ( Col3a1 ) (2^-ddCT Sham vs HTN: 1.5±1.3 vs 5.5±3.1, 1.2±0.8 vs 2.7±1.4, 1.0±0.3 vs 2.2±0.7, respectively). Intestinal immune cell trafficking was observed both in homeostasis (NSD) and disease (HSD). Infiltration of photolabelled Kaede red ( Kred+ ) intestinal immune cells was detected in various organs, namely the mesenteric lymph nodes, spleen, blood and bone marrow, as well as target organs of hypertension, namely the kidney, heart and eye. In the kidney, B-cells (39.9 ± 24.2% (NSD), 66.8 ± 5.8% (HSD) of CD45+ Kred+ cells) and T-cells (32.5 ± 18.3% (NSD), 10.1 ± 4.4% (HSD) of CD45+ Kred+ cells) were among the major migrating populations. Salt-sensitive hypertension was characterized by a dysregulation of the intestinal-renal immune cell axis. Immune cells originating from the intestine migrate and populate various organs, both in physiological homeostasis and in an aberrant manner in salt-sensitive hypertension. Our findings provide insight into mechanisms underlying hypertension-induced organ damage and could argue for interventions targeting intestinal immune cells.